The long range objective of our research is to describe the microcircuitry of the cortex and to determine its relation to cortical function. We will begin these studies in normal adult animals and will then examine how cortical circuitry is modified during development and under conditions of visual deprivation. THe specific goal of this grant is to conduct electron microscopic studies on the cortex in order to understand the synaptic relationships between identified cortical cells. Our knowledge of the circuitry of the cortex is minimal compared to knowledge of the retina's circuitry. New methods, mainly that of intracellular injection and 3-dimensional computer graphics, has enabled us now to obtain a knowledge of the cortex that is as detailed as our present knowledge of the retina. Cells that have been functionally characterized and injected with horseradish peroxidase will be reconstructed at the light level, and these cells will then be examined at the ultrastructural level to identify the cells that are post-synaptic to them. This information is an essential component in determining the function of and interaction between various elements in the cortical circuit. By leading to a detailed description of the mechanism by which the cortex processes information cominng from the retina, these studies will also aid in discovering the specific derangements occurring in dysfunctional states such as amblyopia.